Recent data suggests that use of Pioglitazone for over 2 years may increase a patient’s risk of developing bladder cancer. The drug, created to improve glycemic control in adults with type 2 diabetes mellitus by reducing insulin resistance, is currently under a safety review with the FDA. The review is based on a 10-year observational study of the long-term risk of bladder cancer in approximately 193,000 patients with diabetes who are members of the Kaiser Permanente Northern California health plan. Preliminary data analysis has shown an increasing risk of developing bladder cancer due to Pioglitazone exposure, a risk which reached statistical significance after only 24 months. Until final data from the FDA’s investigation is available, prescribing physicians should pay careful attention to this possible risk.